The objectives of this research are to explore the mechanisms underlying obesity. Two forms of obesity have been chosen for this study. They are: 1) Genetically transmitted obesity in rodents; and, 2) Human obesity as manifest in patients presenting to the medical clinic. Underlying our selection of the genetically transmitted forms of obesity is a broad based knowledge of the mechanisms for transmitting recessively inherited traits. Current information about the biochemical basis of genetics suggests that each gene codes for a specific protein. In animals which inherit traits in a recessive manner, the information coding for a particular protein is defective. If such reasoning applies to the genetically transmitted forms of obesity, then there should be a specific protein which is defective and/or deficient. Identification of the locus and nature of this defect would provide extensive insight into the way in which a biochemical lesion can produce obesity in experimental animals and add greatly to our insight about the transmission of obesity in human beings. The second phase of our research work is directed towards unraveling some facets of the obese state in man. Our approach involves a comparison of the endocrine and metabolic responses in obesity before and after changes in body weight. Since most of the patients are observed after they have become grossly obese, most of our studies have dealt with the effect of weight loss. However, we have also explored some facets of weight gain, since obese patients are gaining rather than losing weight most of the time. From these two approaches, it is hoped to provide new insights which may be of therapeutic value in dealing with the clinical problem presented by debilitating obesity.